Previous studies have demonstrated that the supernatant, non- antigenic fraction obtained from hemolysed sheep red blood cells can act as a specific tolerogen when injected into adult mice. Preliminary work, moreover, indicates that the tolerogen acts by inducing the formation of an inhibitor demonstrable in the serum of tolerant animals rather than by causing irreversible elimination of antigen sensitive precursors of antibody-forming or collaborator cells. Our experiments are designed to determine which cells of the animal are directy involved in responding to tolerogen, to determine the nature and extent of blocking activity associated with tolerance, to delineate the target cells of the blocking material and to provide further information on the chemical nature of the tolerogen. Extension of studies to cell systems other than the heterologous erythrocyte is contemplated. Studies of tolerance induced by soluble factors from erythrocytes may provide clues useful in developing protocols for transplantation, for prevention of autoimmunity, and for regulation of tumor growth.